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Delay to hospital presentation and suboptimal post-percutaneous coronary intervention (PCI) TIMI flow grades are both independently associated with excess mortality in women who suffer ST-segment elevation myocardial infarction (STEMI), according to a study that sought to better define the disproportionate sex gap in STEMI mortality.

Women who present with STEMI are more likely to die than men who present with the same condition, regardless of reperfusion modalities, Edina Cenko, MD, PhD, and colleagues with the University of Bologna in Italy wrote Feb. 15 in the Journal of the American Heart Association. But the reason for that increased risk is unknown, leading Cenko et al. to conduct a study of 2,596 heart attack patients in the ISACS-TC registry.

The authors focused on coronary blood flow, measuring the restoration of circulation after recanalization of an infarct-related artery with the TIMI grading system. TIMI ranks flow grade from 0 to 3, with 0 representing no perfusion and 3 indicating complete perfusion and normal flow.

“Failure to account for sex differences in coronary blood flow after PCI could explain contradictory findings on the rates of mortality among women and men,” Cenko and co-authors wrote. “Abnormal coronary reactivity and microvascular dysfunction are more prevalent among women and may be associated with lower TIMI flow grades and adverse outcomes.”

Thirty-day mortality was the primary outcome of the team’s study, but Cenko et al. also considered TIMI scores. During analysis, female sex was strongly associated with postprocedural TIMI flow grade 0 to 2 (1.68 times greater odds) and a 1.72-fold higher risk of mortality. Using inverse probability of treatment weighting, 30-day mortality was higher in women than in men (4.8 percent vs. 2.5 percent), but that difference wasn’t significant in patients who presented to the hospital within two hours of symptom onset.

The authors also found a significant sex difference in post-PCI TIMI flow grades 0 to 2—there was an 8.8 percent prevalence in women compared to 5 percent prevalence in male patients.

“Female sex has a distinct cardiovascular blood flow reactivity after primary PCI, regardless of time to hospital presentation,” Cenko and colleagues said. “Furthermore, women are more vulnerable to prolonged untreated ischemia. For late STEMI presentations, women have a twofold likelihood of mortality compared with men.”

Differences between men and women seemed to persist even after adjusting for time to hospital presentation, differing treatments and baseline characteristics, and in the study TIMI flow grade and delays to hospital presentation were independently linked to excess mortality in women.

“Sex differences in mortality can be seen only in patients with STEMI,” the authors wrote. “These results provide motivation for adequate consideration of both sexes in experiments and disaggregation of data by sex, which may allow for sex-based comparisons and may inform clinical interventions.”